Project Summary/Abstract The potential benefits and harms of returning genomic results to children and their parents are matters of enduring controversy?especially genomic results for adult-onset conditions that are not medically actionable in childhood. Returning results for adult-onset conditions can spur life-saving preventive measures in the parents of affected children. However, there has been long-standing concern that children who receive a result for an adult-onset condition might experience negative psychosocial outcomes such as distress or altered family functioning. The lack of empirical data to support either position in this controversy prevents policy makers from making evidence-based judgments that balance benefits and harms. We propose to provide this urgently needed data by returning adult- and pediatric-onset genomic results through a supportive clinical program and assessing the associated psychosocial, behavioral and legal impact. Using our experience in returning medically actionable genomic findings to adults in Geisinger's MyCode? Community Health Initiative, and with support from pediatric and adult clinical psychologists and clinician researchers with experience with adolescents at increased cancer risk, we will return results for two adult-onset and 28 pediatric-onset genomic conditions to MyCode pediatric participants and parents. We will conduct a longitudinal, mixed-methods cohort study to assess psychosocial outcomes and health behaviors among participants: with a pathogenic variant in an adult-onset gene (Group 1); with a pathogenic variant in a pediatric-onset gene (Group 2); and without a genomic result (Group 3). This study design will allow us to address three critical research questions: 1) Do children and parents who receive an adult-onset genomic result via a supportive clinical interaction have poorer psychosocial outcomes than their counterparts who receive a pediatric-onset result or no genomic result? 2) How does the receipt of children's genomic information impact their parents' cascade testing and risk reduction decisions? and 3) Does the loss of chance tort doctrine (which allows for recovery of damages when breach of duty caused a reduction in the chance of a favorable outcome) provide an applicable legal framework for deciding whether to return adult-onset genomic findings to children? Data will be gathered longitudinally via quantitative surveys using validated measures of distress, family functioning, and quality of life; qualitative interviews with children and parents in Groups 1 and 2; electronic health records review of parents' uptake of cascade testing and initiation of disease risk reduction procedures; and legal review of relevant case law and legislation. Quantitative analyses will determine whether change in psychosocial and behavioral outcomes from pre- to post-disclosure differs significantly among groups. Qualitative analyses will allow for comparison of themes among those with an adult-onset vs. a pediatric-onset result. Data from this innovative landmark study will guide national and international groups planning to perform genome-scale testing of children, as well as other groups considering population screening for genomic conditions.